Galectin-3
From CFGparadigms
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* has anti-apoptotic activity in its intracellular expression<ref>Saegusa, J. et al. Galectin-3 protects keratinocytes from UVB-induced apoptosis by enhancing AKT activation and suppressing ERK activation. J Invest Dermatol 128, 2403-2411 (2008).</ref> | * has anti-apoptotic activity in its intracellular expression<ref>Saegusa, J. et al. Galectin-3 protects keratinocytes from UVB-induced apoptosis by enhancing AKT activation and suppressing ERK activation. J Invest Dermatol 128, 2403-2411 (2008).</ref> | ||
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| - | Galectin-3 is the only member of the galectin family with an extended N-terminal region composed of tandem repeats of short amino-acid segments (a total of approximately 120 amino acids) connected to a C-terminal CRD. Like other galectins, Galectin-3 lacks a signal sequence required for secretion through the classical secretory pathway, but the protein is released into the extracellular space. <br> | + | Galectin-3 is the only member of the galectin family with an extended N-terminal region composed of tandem repeats of short amino-acid segments (a total of approximately 120 amino acids) connected to a C-terminal CRD. Like other galectins, Galectin-3 lacks a signal sequence required for secretion through the classical secretory pathway, but the protein is released into the extracellular space. <br><br> |
Galectin-3 can oligomerize in the presence of multivalent carbohydrate ligands and is capable of crosslinking glycans on the cell surface, thereby initiating transmembrane signaling events and affecting various cellular functions (reviewed in (1-3)). This ability to self-associate is dependent on the N-terminal region of the protein. | Galectin-3 can oligomerize in the presence of multivalent carbohydrate ligands and is capable of crosslinking glycans on the cell surface, thereby initiating transmembrane signaling events and affecting various cellular functions (reviewed in (1-3)). This ability to self-associate is dependent on the N-terminal region of the protein. | ||
| - | Compared to other galectins, intracellular functions of Galectin-3 have been more extensively documented (reviewed in (4)). In some cases, intracellular proteins with which the protein interacts and which possibly mediate these functions have been identified. Galectin-3 can be phosphorylated at its serine 6 and serine 12 residues (5). | + | <br><br>Compared to other galectins, intracellular functions of Galectin-3 have been more extensively documented (reviewed in (4)). In some cases, intracellular proteins with which the protein interacts and which possibly mediate these functions have been identified. Galectin-3 can be phosphorylated at its serine 6 and serine 12 residues (5). |
Revision as of 17:02, 7 July 2010
Galectin-3...
- is the only member of chimeric subfamily in mammals
- is a very well-studied glycan-binding protein (GBP)
- crystal structure is known
- has unique functions intra- and extra-cellularly, due to unusual N-terminal domain that can participate in protein-protein interactions
- has a unique mode of multimerization
- is the only known anti-apoptotic galectin
- null mice have distinct phenotypes, including alterations in inflammatory and wound-healing responses, and cyst formation in disease[1]
- has unique functions in innate immune response to microbial pathogens
- has been administered in animal models of disease to assess therapeutic potential
- binds distinct cell surface glycoprotein ligands in lymphocytes compared to Galectin-16
- expression is involved in growth modulation[2]
- has anti-apoptotic activity in its intracellular expression[3]
Galectin-3 is the only member of the galectin family with an extended N-terminal region composed of tandem repeats of short amino-acid segments (a total of approximately 120 amino acids) connected to a C-terminal CRD. Like other galectins, Galectin-3 lacks a signal sequence required for secretion through the classical secretory pathway, but the protein is released into the extracellular space.
Galectin-3 can oligomerize in the presence of multivalent carbohydrate ligands and is capable of crosslinking glycans on the cell surface, thereby initiating transmembrane signaling events and affecting various cellular functions (reviewed in (1-3)). This ability to self-associate is dependent on the N-terminal region of the protein.
Compared to other galectins, intracellular functions of Galectin-3 have been more extensively documented (reviewed in (4)). In some cases, intracellular proteins with which the protein interacts and which possibly mediate these functions have been identified. Galectin-3 can be phosphorylated at its serine 6 and serine 12 residues (5).
Contents |
CFG Participating Investigators contributing to the understanding of this paradigm
CFG Participating Investigators (PIs) contributing to the understanding of Galectin-3 include: Linda Baum, Susan Bellis, Roger Chammas, Richard Cummings, James Dennis, Margaret, Huflejt, Fu-Tong Liu, Joshiah Ochieng, Noorjahan Panjawani, Mauro Perretti, Avram Raz, James Rini, Maria Roque-Barreira, Sachiko Sato, Tariq Sethi, Irma van Die, Gerardo Vasta, John Wang, Paul Winyard
Progress toward understanding this GBP paradigm
Carbohydrate ligands
Cellular expression of GBP and ligands
Biosynthesis of ligands
Structure
Biological roles of GBP-ligand interaction
CFG resources used in investigations
The best examples of CFG contributions to this paradigm are described below, with links to specific data sets. For a complete list of CFG data and resources relating to this paradigm, see the CFG database search results for Galectin-3.
Glycan profiling
Glycogene microarray
Knockout mouse lines
Galectin-3 knockout mice were phenotyped by the CFG and continue to be used by investigators to study the biological functions of Galectin-3.
Glycan array
Investigators have used CFG carbohydrate compounds and glycan arrays to study ligand binding specificity of Galectin-3 (for example, click here). To see all glycan array results for Galectin-3, click here.
Related GBPs
None in mammals, homologues in invertebrates.
References
- ↑ Chiu, M.G. et al. Galectin-3 associates with the primary cilium and modulates cyst growth in congenital polycystic kidney disease. Am J Pathol 169, 1925-1938 (2006).
- ↑ Baptiste, T.A., James, A., Saria, M. & Ochieng, J. Mechano-transduction mediated secretion and uptake of Galectin-3 in breast carcinoma cells: implications in the extracellular functions of the lectin. Exp Cell Res 313, 652-664 (2007).
- ↑ Saegusa, J. et al. Galectin-3 protects keratinocytes from UVB-induced apoptosis by enhancing AKT activation and suppressing ERK activation. J Invest Dermatol 128, 2403-2411 (2008).
Acknowledgements
The CFG is grateful to the following PIs for their contributions to this wiki page: Linda Baum, Richard Cummings, Michael Demetriou, Fu-Tong Liu
